Rationale NICE provide evidence-based recommendations and guidance to the NHS regarding newly licensed drugs. Positive guidance for the use of mepolizumab, an anti IL-5 mAb, was issued for adults with severe refractory eosinophilic asthma in a sub-population who 1) have had eosinophils of ≥300 cells per microlitre (0.30 × 10⁹/L) within the previous twelve months, and 2) have had ≥4 asthma exacerbations needing systemic corticosteroids in the previous 12 months, or have had continuous oral corticosteroids (of at least the equivalent of prednisolone 5 mg/day) for six months previously. A post-hoc meta-analysis of 3 pivotal phase III studies was done to inform healthcare professionals’ understanding of mepolizumab’s efficacy in this subgroup.

Methods Three randomised double-blind, placebo-controlled studies (DREAM [NCT01000506], MENSA [NCT01691521], SIRIUS [NCT01691508]), using the licensed 100 mg SC dose or the bioequivalent 75 mg IV dose of mepolizumab, were identified. Both treatment arms were combined for analysis purposes. Data for key outcome measures (exacerbations, asthma control, and health-related quality of life) included within these trials was analysed in the sub-population and combined using the inverse-variance method. Data from SIRIUS was included in a sensitivity analysis due to differences in design and inclusion criteria from DREAM and MENSA.

Results 228 patients were included in the meta-analysis from DREAM and MENSA, 289 including SIRIUS. The mean patient age was 52.1 and 51.4 years, respectively, with a respective 60% and 61% female. In the meta-analysis of the UK NICE-specific subpopulation of DREAM and MENSA, a 53% (95% CI: 0.36, 0.62; p<0.001) reduction in clinically significant exacerbations was seen, with a 49% (95% CI: 0.01, 0.64, p<0.001) reduction including sensitivity analysis with SIRIUS. An improvement in ACQ score of −0.50 (95% CI: −0.73, −0.27; p<0.001) and −0.53 (95% CI: −0.73, −0.33; p<0.001) was observed, respectively. SGRQ was used as an outcome measure in MENSA and SIRIUS only, showing an improvement in score of −7.3 (95% CI: −11.1, −3.5, p<0.001).

Conclusion In the NICE sub-population, mepolizumab showed clinically meaningful and statistically significant effectiveness. These Results aim to inform UK healthcare professionals’ understanding of the likely treatment effect of mepolizumab in this sub-population.

Funding GSK (NCT01000506, NCT01691521, NCT01691508).